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Molecular landscape of the fungal plasma membrane and implications for antifungal action

Author

Listed:
  • Jennifer Jiang

    (The State University of New Jersey
    The State University of New Jersey)

  • Mikhail V. Keniya

    (Hackensack Meridian Health-Center for Discovery and Innovation)

  • Anusha Puri

    (The State University of New Jersey
    The State University of New Jersey)

  • Xueying Zhan

    (Carnegie Mellon University)

  • Jeff Cheng

    (The State University of New Jersey
    The State University of New Jersey)

  • Huan Wang

    (The State University of New Jersey)

  • Gigi Lin

    (City University of New York-Hunter College)

  • Yun-Kyung Lee

    (The State University of New Jersey
    The State University of New Jersey)

  • Nora Jaber

    (The State University of New Jersey
    The State University of New Jersey
    The State University of New Jersey)

  • Caifeng Zhao

    (The State University of New Jersey)

  • Cynthia Pang

    (The State University of New Jersey
    The State University of New Jersey)

  • Yasmine Hassoun

    (Hackensack Meridian Health-Center for Discovery and Innovation)

  • Haiyan Zheng

    (The State University of New Jersey)

  • Erika Shor

    (Hackensack Meridian Health-Center for Discovery and Innovation
    Hackensack Meridian School of Medicine)

  • Zheng Shi

    (The State University of New Jersey)

  • Sang-Hyuk Lee

    (The State University of New Jersey
    The State University of New Jersey)

  • Min Xu

    (Carnegie Mellon University)

  • David S. Perlin

    (Hackensack Meridian Health-Center for Discovery and Innovation)

  • Wei Dai

    (The State University of New Jersey
    The State University of New Jersey)

Abstract

Fungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their native structure and spatial distribution remain poorly characterized. Herein, we employ an integrative approach to investigate the organization of plasma membrane protein complexes in Candida glabrata, focusing on two abundant and essential membrane proteins, the β-(1,3)-glucan synthase (GS) and the proton pump Pma1. We show that treatment with caspofungin, an echinocandin antifungal that targets GS, disrupts the native distribution of membrane protein complexes and alters membrane biophysical properties. Perturbation of the sphingolipid biosynthesis further modulates drug susceptibility, revealing that the lipid environment plays an integral role in membrane protein organization and GS-echinocandin interactions. Our work highlights the importance of characterizing membrane proteins in their native context to understand their functions and inform the development of novel antifungal therapies.

Suggested Citation

  • Jennifer Jiang & Mikhail V. Keniya & Anusha Puri & Xueying Zhan & Jeff Cheng & Huan Wang & Gigi Lin & Yun-Kyung Lee & Nora Jaber & Caifeng Zhao & Cynthia Pang & Yasmine Hassoun & Haiyan Zheng & Erika , 2025. "Molecular landscape of the fungal plasma membrane and implications for antifungal action," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64171-x
    DOI: 10.1038/s41467-025-64171-x
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    References listed on IDEAS

    as
    1. Peng Zhao & Chaoran Zhao & Dandan Chen & Caihong Yun & Huilin Li & Lin Bai, 2021. "Structure and activation mechanism of the hexameric plasma membrane H+-ATPase," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
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